Sugibayashi Kenji, Yamamoto Nao, Itakura Shoko, Okada Akie, Hijikuro Ichiro, Todo Hiroaki
Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Farnex Co., Inc., Tokyo Institute of Technology Yokohama Venture Plaza.
Chem Pharm Bull (Tokyo). 2020;68(11):1025-1033. doi: 10.1248/cpb.c20-00333.
We examined the physicochemical and biochemical properties of mono-O-(5,9,13-trimethyl-4-tetradecenyl)glycerol ester (MGE), including ease of handling, high bioadhesiveness, quick and stable in vivo self-organization (forming a non-lamellar lyotropic liquid crystal [NLLC]), and high biomembrane permeation enhancement. We prepared MGE oral mucosa-applied spray preparations containing triamcinolone acetonide (TA), which is widely used in the treatment of stomatitis, and we examined the usefulness of the MGE preparations compared with commercially available oral mucosal application preparations containing 2,3-dihydroxypropyl oleate (1-mono(cis-9-octadecenoyl)glycerol (GMO) (previously studied as an NLLC-forming lipid) preparation. As a result, the MGE preparation applied to the oral mucosa can rapidly formed an NLLC with reverse hexagonal or cubic structures, or a mixture, on contact with water. In addition, by adding hydroxypropyl cellulose to the MGE preparation, similar retention properties on the oral mucous membrane were obtained to that using marketed drug preparations. Furthermore, the MGE spray formulation on the oral mucosa showed an equivalent or higher TA release as well as oral mucous membrane permeability compared with commercial formulations. Because MGE forms a stable NLLC and is easy to handle compared with GMO, MGE was considered to be a useful pharmaceutical additive for a spray preparation applied to the oral mucosa in combination.
我们研究了单 -O-(5,9,13 - 三甲基 -4 - 十四碳烯基)甘油酯（MGE）的物理化学和生化特性，包括易于处理、高生物粘附性、在体内快速且稳定地自我组织（形成非层状溶致液晶 [NLLC]）以及高生物膜渗透增强作用。我们制备了含有广泛用于治疗口腔炎的曲安奈德（TA）的MGE口腔黏膜应用喷雾剂制剂，并与含有油酸2,3 - 二羟丙酯（1 - 单（顺式 -9 - 十八碳烯酰基）甘油（GMO）（先前作为形成NLLC的脂质进行研究）的市售口腔黏膜应用制剂相比，研究了MGE制剂的实用性。结果，应用于口腔黏膜的MGE制剂在与水接触时可迅速形成具有反六边形或立方结构或混合物的NLLC。此外，通过向MGE制剂中添加羟丙基纤维素，获得了与市售药物制剂在口腔黏膜上相似的保留特性。此外，与市售制剂相比，口腔黏膜上的MGE喷雾制剂显示出相当或更高的TA释放以及口腔黏膜渗透性。由于MGE与GMO相比形成稳定的NLLC且易于处理，因此MGE被认为是一种用于联合应用于口腔黏膜的喷雾制剂的有用药物添加剂。
